Deletion of the carboxyl-terminal exons of K-sam/FGFR2 by short homology-mediated recombination, generating preferential expression of specific messenger RNAs

The K-sam gene was first identified as an amplified gene from human gastric cancer cell line KATOIII, and its product is identical to fibroblast growt h factor receptor 2. The K-sam gene is located on human chromosome 10q26 an d is preferentially amplified in the poorly differentiated types, especiall y in the scirrhous type, of gastric cancers, During the course of studies o n the structural characterization of the amplification units, we found that the carboxyl-terminal exons of K-sam were deleted in three of four of the scirrhous type of gastric cancer cell lines, These deletions generate prefe rential expression of mRNAs encoding K-sam proteins lacking the carboxyl-te rminal region containing the tyrosine residues at positions 780, 784, and 8 13. The carboxyl-terminal region has been reported to have a sequence requi red for the inhibition of NIH3T3 transformation, indicating that cells with amplification of the truncated K-sam gene have a growth advantage during t he carcinogenic process for the scirrhous type of gastric cancers. This is the first report showing the deletion of the carboxyl-terminal exons of the receptor-type of the protein tyrosine kinase gene, Sequence analysis of th e DNA sequences surrounding the deletion junctions shows the presence of un ique sequences and indicates the involvement of short homology-mediated rec ombination in the generation of these deletions.